You are here

  • Home
  • Archive
  • Volume 40, Issue 8
  • Individual and family characteristics associated with protein truncating BRCA1 and BRCA2 mutations in an Ontario population based series from the Cooperative Family Registry for Breast Cancer Studies

Article Text

Article menu
Download PDFPDF
Electronic letters
Individual and family characteristics associated with protein truncating BRCA1 and BRCA2 mutations in an Ontario population based series from the Cooperative Family Registry for Breast Cancer Studies
  1. H Ozcelik1,3,4,
  2. J A Knight2,5,
  3. G Glendon7,
  4. H Yazici1,
  5. N Carson9,
  6. P J Ainsworth10,
  7. S A M Taylor11,
  8. H Feilotter11,
  9. R F Carter12,
  10. N F Boyd5,8,
  11. I L Andrulis1,3,4,6,7,
  12. for the Ontario Cancer Genetics Network
  1. 1Fred A Litwin Centre for Cancer Genetics, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
  2. 2Division of Epidemiology of Biostatistics, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
  3. 3Samuel Lunenfeld Research Institute, and Department of Pathology and Laboratory Medicine, University of Toronto, Ontario, Canada
  4. 4Mount Sinai Hospital, and Department of Pathology and Laboratory Medicine, University of Toronto, Ontario, Canada
  5. 5Department of Public Health Sciences, University of Toronto, Ontario, Canada
  6. 6Department of Molecular and Medical Genetics, University of Toronto, Ontario, Canada
  7. 7Division of Research, Ontario Cancer Genetics Network, Cancer Care Ontario, Ontario, Canada
  8. 8Division of Epidemiology and Statistics, Ontario Cancer Institute, Toronto, Ontario, Canada
  9. 9Department of Genetics, Children’s Hospital of Eastern Ontario, Ottawa, Ontario, Canada
  10. 10Molecular Diagnostic Laboratory, London Health Sciences Centre and University of Western Ontario, London, Ontario, Canada
  11. 11Department of Pathology, Queen’s University and Kingston General Hospital, Kingston, Ontario, Canada
  12. 12Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada
  1. Correspondence to:
 Dr I L Andrulis, 600 University Avenue, Room 984, Toronto, Ontario M5G 1X5 Canada; 
 Andrulis{at}mshri.on.ca

https://doi.org/10.1136/jmg.40.8.e91

Statistics from Altmetric.com

    Request Permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

    Studies using multicase breast cancer families led to the mapping and eventual cloning of the two susceptibility genes for breast or ovarian cancer or both, BRCA1(MIM 113705) and BRCA2 (MIM 600185).1,2 In early studies attempting to characterise the clinical impact of mutations in these genes, investigators continued to analyse large multicase families.3 More recently, groups have focused on patients with breast cancer unselected for strong family cancer history to make their findings more generally applicable.4–7 With the broadening of study participant ascertainment, there has been a drop in the estimates of lifetime breast cancer penetrance attributable to BRCA1 and BRCA2 from greater than 80% initially to values as low as 40%.3,8

    Attempts to characterise the range and frequency of BRCA1 and BRCA2 mutations in breast cancer families have also been complicated by the different molecular techniques used to identify them. Owing to the large size, multiexonic nature, and lack of any universally identified mutational hot spots in the genes, few studies have conducted a thorough investigation of the presence of mutations in both genes. Also, there have been some missense mutations of unknown clinical significance identified (Breast Cancer Information Core). There is also some evidence that the position of the mutation in the BRCA2 gene may influence the clinical manifestation of cancer risk, which would further complicate the interpretation of findings from studies that use targeted molecular analysis.9

    Molecular studies of cases ascertained through a population based design more accurately reflect the range and frequency of BRCA1 and BRCA2 mutations in a specific population. The Ontario Familial Breast Cancer Registry (OFBCR)10,11 is one of six sites participating in the international Cooperative Family Registry for Breast Cancer Studies (CFRBCS). The OFBCR is a population based breast cancer registry, the purpose …

    View Full Text